Skip to main content
SpringerLink
Log in

Case report on two-cathinones abuse: MPHP and N-ethyl-4′methylnorpentedrone, with a fatal outcome

  • Case Report
  • Published:
Forensic Toxicology Aims and scope Submit manuscript

Abstract

Purpose

The correlation between the rising consumption of new psychoactive drugs (NPS), including that of cathinones, and the occurrence of death has not been sufficiently backed up with published analytic data. In fact, the identification of cathinones in human biological samples remains difficult mainly due to the diversity of these substances and their high turnover. In this context, this manuscript aims at documenting a fatal case of a 39-year-old man: autopsy findings consisted in unspecific asphyxic syndrome.

Methods

Blood ethanol concentration determination and toxicological screenings were performed using gas chromatography with flame ionization detection, liquid chromatography with diode array detection and gas chromatography with mass spectrometry detection, respectively. Liquid chromatography with high-resolution mass spectrometry detection allowed the confirmation of the presence of NPS and the subsequent metabolic study.

Results

The analyses have shown the presence of ethanol, tetrahydrocannabinol and two cathinones, 4′-methyl-α-pyrrolidinohexanophenone (MPHP) and N-ethyl-4′-methylnorpentedrone (4-MEAP). MPHP/4-MEAP concentrations were 47/1.6, 97/3.5 and 2380/49,700 µg/L in femoral blood, cardiac blood and urine, respectively. The in vitro metabolic study has highlighted the presence of five metabolites derived from MPHP and three from 4-MEAP but only two metabolites of these products have been detected in biological samples. The 4′-carboxy-PHP, one of the metabolites of MPHP, was detected in every biological sample with higher chromatographic signals than MPHP itself.

Conclusions

The number of fatalities related to cathinones use is expected to increase in the coming years. This manuscript reports useful analytical data about MPHP, one of its metabolites (4′-carboxy-PHP) and 4-MEAP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Logan BK, Mohr ALA, Friscia M, Krotulski AJ, Papsun DM, Kacinko SL, Ropero-Miller JD, Huestis MA (2017) Reports of adverse events associated with use of novel psychoactive substances, 2013-2016: a review. J Anal Toxicol 41(7):573–610

    Article  CAS  Google Scholar 

  2. EMCDDA (2017) European drug report 2017: trends and developments. Publications Office of the European Union, Luxembourg

    Google Scholar 

  3. European Monitoring Centre for Drugs and Drug Addiction (2018) European drug report 2018: trends and developments. Publications Office of the European Union, Luxembourg

    Google Scholar 

  4. Sauer C, Hoffmann K, Schimmel U, Pters FT (2011) Acute poisoning involving the pyrrolidinophenone-type designer drug 4′-methyl-alpha-pyrrolidinohexaphenone (MPHP). Forensic Sci Int 208:e20–e25

    Article  CAS  Google Scholar 

  5. Zaami S, Giogetti R, Pichini S, Pantano F, Marinelli E, Busardo FP (2018) Synthetic cathinones related fatalities: an update. Eur Rev Med Pharmacol Sci 22:268–274

    CAS  PubMed  Google Scholar 

  6. Valente MJ, Guedes de Pinho P, de Lourdes Bastos M, Carvalho F, Carvalho M (2014) Khat and synthetic cathinones: a review. Arch Toxicol 88:15–45

    Article  CAS  Google Scholar 

  7. Martinez-Clemente J, Escubedo E, Pubill D, Camarasa J (2012) Interaction of mephedrone with dopamine and serotonin targets in rats. Eur Neurospychopharmacol 22:231–236

    Article  CAS  Google Scholar 

  8. Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (2012) The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37:1192–1203

    Article  CAS  Google Scholar 

  9. Winstock A, Mitcheson I, Ramsey J, Davies S, Puchnarewicz M, Marsden J (2011) Mephedrone: use, subjective effects and health risks. Addiction 106:1991–1996

    Article  Google Scholar 

  10. Schifano F, Orsolini L, Duccio Papanti G, Corkery JM (2015) Novel psychoactive substances of interest for psychiatry. World Psychiatry 14:15–26

    Article  Google Scholar 

  11. German CI, Fleckenstein AE, Hanson GR (2014) Bath salts and synthetic cathinones: an emerging designer drug phenomenon. Life Sci 97:2–8

    Article  CAS  Google Scholar 

  12. Morris H (2010) Mephedrone: the phantom menace. Vice 17:98–100

    Google Scholar 

  13. Loi B, Claridge H, Goodair C, Chiappini S, Gimeno Clemente C, de Schifano F (2015) Deaths of individuals aged 16–24 in UK using mephedrone. Human Psychopharmacol 30:225–232

    Article  Google Scholar 

  14. Warrick B, Wilson J, Hedge M, Freeman S, Leonard K, Aaron C (2012) Lethal serotonin syndrome after methylone and butylone ingestion. J Med Toxicol 8:65–68

    Article  Google Scholar 

  15. Barrios L, Grison-Hernando H, Boels D, Bouquie R, Monteil-Ganiere C, Clement R (2016) Death following ingestion of methylone. Int J Legal Med 130:381–385

    Article  CAS  Google Scholar 

  16. Meltzer PC, Butler D, Deschamps JR, Madras BK (2006) 1-(4-Methylphenly)-2-pyrrolidin-1-yl-pentan-1-one (pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. J Med Chem 49:1420–1432

    Article  CAS  Google Scholar 

  17. Kelly JP (2011) Cathinone derivatives: a review of their chemistry, pharmacology and toxicology. Drug Test Anal 3:439–453

    Article  CAS  Google Scholar 

  18. Servin A, Fauquet JP, Jacquot C, Rapin JR (1978) Effects of pyrovalerone on peripheral noradrenergic mechanisms. Biochem Pharmacol 27:1693–1694

    Article  CAS  Google Scholar 

  19. Fauquet JP, Morel E, Demarty C, Rapin JR (1976) Role of central catecholamines in the psychostimulant activity of pyrovalerone. Arch Int Pharmacodyn Ther 224:325–327

    CAS  PubMed  Google Scholar 

  20. Majchrzak M, Celinski R, Kus P, Kowalska T, Sajewicz M (2018) The newest cathinones derivatives as designer drugs: an analytical and toxicological review. Forensic Toxicol 36:33–50

    Article  CAS  Google Scholar 

  21. Rojkiewicz M, Kuś P, Kusz J, Książek M (2018) Spectroscopic and crystallographic characterization of two cathinone derivatives: 1-(4-fluorophenyl)-2-(methylamino)pentan-1-one (4-FPD) hydrochloride and 1-(4-methylphenyl)-2-(ethylamino)pentan-1-one (4-MEAP) hydrochloride. Forensic Toxicol 36(1):141–150

    Article  CAS  Google Scholar 

  22. Varma A, Patel N, Ford L, Jones R, Allister Vale J (2017) Misuse of 2-(ethylamino)-1-(4-methylphenyl)-1-pentanone (4-MEAP), a synthetic cathinone. Clin Toxicol 55(3):231–232

    Article  CAS  Google Scholar 

  23. Hamby D, Burnett A, Jablonsky M, Twamley B, Kavanagh PV, Gardner EA (2015) Identification of 2-(ethylamino)-1-(4-methylphenyl)-1-pentanone (4-MEAP), a new “legal high” sold by an internet vendor as 4-methyl pentedrone. J Forensic Sci 60(3):721–726

    Article  CAS  Google Scholar 

  24. UNODC EWA (2019) Current NPS Threats, vol. 1 March 2019. Consulted on http://www.unodc.org/pdf/opioids-crisis/Current_NPS_Threats_Volume_I.pdf

  25. Turcant A, Prémel-Cabic A, Cailleux A, Allain P (1991) Toxicological screening of drugs by microbore high-performance liquid chromatography with photodiode-array detection and ultraviolet spectral library searches. Clin Chem 37(7):1210–1215

    CAS  PubMed  Google Scholar 

  26. Richeval C, Gicquel T, Hugbart C, Le Dare B, Allorge D, Morel I, Gaulier JM (2017) In vitro characterization of NPS metabolites produced by human liver microsomes and the HepaRG cell line using liquid chromatography-high resolution mass spectrometry (LC–HRMS) analysis: application to furanyl fentanyl. Curr Pharm Biotechnol 18(10):806–814

    Article  CAS  Google Scholar 

  27. Kronstrand R, Brinkhagen L, Birath-Karlsson C, Roman M, Josefsson M (2014) LC-QTOF-MS as a superior strategy to immunoassay for the comprehensive analysis of synthetic cannabinoids in urine. Anal Bioanal Chem 406:3599–3609

    Article  CAS  Google Scholar 

  28. Boumrah Y, Humbert L, Phanithavong M, Khimeche K, Dahmania A, Allorge D (2016) In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS. Drug Test Anal 8:248–526

    Article  CAS  Google Scholar 

  29. Kintz P, Richeval C, Jamey C, Ameline A, Allorge D, Gaulier JM, Raul JS (2017) Detection of the designer benzodiazepine metizolam, in urine and preliminary data on its metabolism. Drug Test Anal 9(7):1026–1033

    Article  CAS  Google Scholar 

  30. Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165(2–3):216–224

    Article  CAS  Google Scholar 

  31. Antignac JP, de Wasch K, Monteau F, De Brabander H, Andre F, Le Bizec B (2005) The ion suppression phenomenon in liquid chromatography–mass spectrometry and its consequences in the field of residue analysis. Anal Chim Acta 529:129–136

    Article  CAS  Google Scholar 

  32. Wille SMR, Peters FT, Di Fazio V, Samyn N (2011) Practical aspects concerning validation and quality control for forensic and clinical bioanalytical quantitative methods. Accred Qual Assur 16:279–292

    Article  Google Scholar 

  33. Allibe N, Richeval C, Phanithavong M, Faure A, Allorge D, Paysant F, Stanke-Labesque F, Eysseric-Guerin H, Gaulier JM (2018) Fatality involving ocfentanil documented by identification of metabolites. Drug Test Anal 10(6):995–1000

    Article  CAS  Google Scholar 

  34. Ameline A, Richeval C, Gaulier JM, Raul JS, Kintz P (2018) Detection of the designer benzodiazepine flunitrazolam in urine and preliminary data on its metabolism. Drug Test Anal. https://doi.org/10.1002/dta.2480

    Article  PubMed  Google Scholar 

  35. Springer D, Peters FT, Fitschi G, Maurer HH (2003) New designer drug 4′-methyl-α-pyrrolidinohexaphenone: studies on its metabolism and toxicological detection in urine using gas chromatography–mass spectrometry. J Chromatogr B 789:79–91

    Article  CAS  Google Scholar 

  36. Westphal F, Junge T, Rösner P, Fitschi G, Klein B, Girreser U (2007) Mass spectral and NMR spectral data of two new designer drugs with an α-aminophenone structure: 4′-methyl-α-pyrrolidinohexaphenone and 4′-methyl-α-pyrrolidinobutyrophenone. Forensic Sci Int 169:34–42

    Article  Google Scholar 

  37. Shintani-Ishida K, Kakuichi Y, Ikegaya H (2016) Successful quantification of 4′-methyl-α-pyrrolidinohexaphenone (MPHP) in human urine using LC-TOF-MS in an autopsy case. Forensic Toxicol 34:398–402

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Pharmacologie-toxicologie, Centre Régional de Pharmacovigilance, CHU Angers, Angers, France

    Lelievre Benedicte, Ferec Severine & Drevin Guillaume

  2. Unité Fonctionnelle de Toxicologie, CHU Lille, Lille, France

    Richeval Camille, Coulon Audrey, Allorge Delphine & Gaulier Jean-Michel

  3. University of Lille, EA 4483, IMPECS, IMPact de l’Environnement Chimique sur la Santé Humaine, Lille, France

    Richeval Camille, Allorge Delphine & Gaulier Jean-Michel

  4. Service de Médecine Légale, CHU Angers, Angers, France

    Iwanikow Deborah, Brofferio Morgan & Jousset Nathalie

  5. Centre Antipoison-Toxicovigilance, CHU Angers, Angers, France

    Deguigne Marie & Boels David

  6. Service de Pharmacologie-Toxicologie Clinique, CHU Nantes, Nantes, France

    Boels David

Authors
  1. Lelievre Benedicte
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richeval Camille
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Coulon Audrey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iwanikow Deborah
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Brofferio Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Deguigne Marie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Boels David
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Allorge Delphine
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ferec Severine
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Drevin Guillaume
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jousset Nathalie
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gaulier Jean-Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lelievre Benedicte.

Ethics declarations

Conflict of interest

There are no financial, or other, relations that could lead to a conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals that were performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Benedicte, L., Camille, R., Audrey, C. et al. Case report on two-cathinones abuse: MPHP and N-ethyl-4′methylnorpentedrone, with a fatal outcome. Forensic Toxicol 38, 243–254 (2020). https://doi.org/10.1007/s11419-019-00486-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11419-019-00486-x

Keywords

Search

Navigation